ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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50 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Prognostic Value of Focal Adhesion Kinase (FAK) in Human Solid Carcinomas: A Meta-Analysis.PloS one · 2016Pooled it
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- PTX3 facilitates tumor cell migration and invasion through the miR-1255b-2-3p/CYP2J2 axis in oral squamous cell carcinoma.Cancer cell international · 2026Article
- IS THERE A PROGNOSTIC ROLE OF FOCAL ADHESION KINASE AND CD8 IN SQUAMOUS CELL HEAD AND NECK CANCER TREATED WITH RADIOTHERAPY?Acta clinica Croatica · 2025Article
- Therapeutic potential of isochlorogenic acid A fromFrontiers in immunology · 2025Article
- Pharmacoproteogenomic approach identifies on-target kinase inhibitors for cancer drug repositioning.In vitro cellular & developmental biology. Animal · 2024Article
- ERK5 suppression overcomes FAK inhibitor resistance in mutant KRAS-driven non-small cell lung cancer.EMBO molecular medicine · 2024Article
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- FAK Drives Resistance to Therapy in HPV-Negative Head and Neck Cancer in a p53-Dependent Manner.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Roles of clinical application of lenvatinib and its resistance mechanism in advanced hepatocellular carcinoma (Review).American journal of cancer research · 2024Review
- Focal adhesion kinase confers lenvatinib resistance in hepatocellular carcinoma via the regulation of lysine-deficient kinase 1.Molecular carcinogenesis · 2024Article
- Focal adhesion kinase: from biological functions to therapeutic strategies.Experimental hematology & oncology · 2023Review
- Histology Specific Molecular Biomarkers: Ushering in a New Era of Precision Radiation Oncology.Seminars in radiation oncology · 2023Review
- MFI2 upregulation promotes malignant progression through EGF/FAK signaling in oral cavity squamous cell carcinoma.Cancer cell international · 2023Article
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- Lung transcriptome of nonhuman primates exposed to total- and partial-body irradiation.Molecular therapy. Nucleic acids · 2022Article
- Focal adhesion kinase priming in pancreatic cancer, altering biomechanics to improve chemotherapy.Biochemical Society transactions · 2022Article
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- Radiotherapy resistance: identifying universal biomarkers for various human cancers.Journal of cancer research and clinical oncology · 2022Review
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18 authors at 2 institutions in 1 country.
Funding
Abstract
purposeHead and neck squamous cell carcinoma (HNSCC) is commonly treated with radiotherapy, and local failure after treatment remains the major cause of disease-related mortality. To date, human papillomavirus (HPV) is the only known clinically validated, targetable biomarkers of response to radiation in HNSCC. EXPERIMENTAL
designWe performed proteomic and transcriptomic analysis of targetable biomarkers of radioresistance in HPV-negative HNSCC cell lines in vitro, and tested whether pharmacologic blockade of candidate biomarkers sensitized cells to radiotherapy. Candidate biomarkers were then investigated in several independent cohorts of patients with HNSCC.
resultsIncreased expression of several targets was associated with radioresistance, including FGFR, ERK1, EGFR, and focal adhesion kinase (FAK), also known as PTK2. Chemical inhibition of PTK2/FAK, but not FGFR, led to significant radiosensitization with increased G2-M arrest and potentiated DNA damage. PTK2/FAK overexpression was associated with gene amplification in HPV-negative HNSCC cell lines and clinical tumors. In two independent cohorts of patients with locally advanced HPV-negative HNSCC, PTK2/FAK amplification was highly associated with poorer disease-free survival (DFS; P = 0.012 and 0.034). PTK2/FAK mRNA expression was also associated with worse DFS (P = 0.03). Moreover, both PTK2/FAK mRNA (P = 0.021) and copy number (P = 0.063) were associated with DFS in the Head and Neck Cancer subgroup of The Cancer Genome Atlas.
conclusionsProteomic analysis identified PTK2/FAK overexpression is a biomarker of radioresistance in locally advanced HNSCC, and PTK2/FAK inhibition radiosensitized HNSCC cells. Combinations of PTK2/FAK inhibition with radiotherapy merit further evaluation as a therapeutic strategy for improving local control in HPV-negative HNSCC. Clin Cancer Res; 22(18); 4643-50. ©2016 AACR.
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